Experience-dependent increase in cAMP-responsive element binding protein in synaptic and nonsynaptic mitochondria of the rat hippocampus

Cyclic AMP-responsive element binding protein (CREB) plays a pivotal role i n the formation of long-term memory in Drosophila, Aplysia, mice and rats. Recently, we were able to demonstrate that CREB and its serine 133 phosphor ylated form p-CREB ae localized in synaptic and nonsynaptic mitochondria of the rat brain. Here we report on the effect of a one-trial inhibitory avoi dance training procedure on mitochondrial CREB from the rat hippocampus. Th is aversively motivated training task is associated with a time-dependent i ncrease (34-35%) in both p-CREB and CREB immunoreactivities detected in syn aptic mitochondria of the hippocampus. In nonsynaptic mitochondria, p-CREB levels increased in both trained and shocked animals. In addition to CREB, two CRE-element binding repressors, CREB-2 and CREM-1, were also detected i n purified brain mitochondria. No changes were observed in CREB-2 and CREM- 1 immunoreactivities in hippocampal synaptic mitochondria after an inhibito ry avoidance training. Taken together the present findings represent the fi rst evidence showing that brain mitochondrial CREB may participate in plast icity-dependent changes associated with a behavioural training procedure.